[0001] The present invention relates to a saccharide for supplementing energy to a living
body (designated as "SACCHARIDE" hereinafter) and its preparation, more particularly,
it relates to SACCHARIDE which comprises neotrehalose, as well as to a composition
for supplementing energy to a living body (designated as "COMPOSITION" hereinafter)
which contains neotrehalose as effective ingredient.
[0002] Glucose and fructose, which exhibit reducing properties, have been used from old
times as SACCHARIDE. These saccharides are, however, unstable because of their inherent
reducing properties, and usually, the unstableness is more augmented in the presence
of other nutritional substances such as amino acids and vitamins.
[0003] Therefore, there has been a great demand for the establishment of SACCHARIDE selected
from the group consisting of non-reducing saccharides with a satisfiable stability,
for example, xylitol, sorbitol, maltitol, lactitol, sucrose and trehalose. The monosaccharide
alcohols (hydrogenated monosaccharides) such as xylitol and sorbitol have, however,
a drawback: They give an acute diarrhea when the dose and administration method are
mistaken. As described in Japanese Patent Publication Nos.13,699/72 and 42,506/72,
the disaccharide alcohols (hydrogenated disaccharides) such as maltitol and lactitol
are not readily metabolized and utilized
in vivo, and actually, they have been used as a low-caloric sweetener and not suitable for
SACCHARIDE. Sucrose has a drawback: It is readily hydrolyzed under acidic conditions
into glucose and fructose which exhibit reducing properties, and this hinders the
storage stability. As Japanese Patent Laid-Open No.240,758/88 describes "Trehalose
is a low-caloric sweetener which is not readily metabolized and absorbed by the human
body." and "Trehalose is not readily hydrolyzed by enzymes such as amylases.", it
has been recognized that trehalose is a saccharide which does not release energy in
a living body, and that a large amount of trehalose preparation is very difficult
and the preparation has not been studied in detail.
[0004] There has been a great demand for the realization of SACCHARIDE which is free of
reducing properties, satisfiable in storage stability, and usable in a variety of
fields, as well as for the realization of SACCHARIDE which contains neotrehalose as
effective ingredient.
[0005] The present inventors have studied SACCHARIDEs. In particular, the present inventors
studied non-reducing disaccharides such as trehalose and its relating substances.
[0006] As a result, the present inventors found that unexpectedly unlike trehalose (α,α-trehalose)
and isotrehalose (β,β-trehalose), neotrehalose (O-α-D-glucopyranosyl β-D-glucopyranoside
or α,β-trehalose) was readily metabolized and utilized by a living body into energy,
and that neotrehalose was a novel SACCHARIDE which can be used in a variety of fields
because of its stability and non-reducing properties, and the present inventors accomplished
COMPOSITION which contains neotrehalose as effective ingredient. Thus, the present
inventors accomplished the present invention. Since neotrehalose has a relatively-high
storage stability and dose not have reducing properties, the present COMPOSITION can
be advantageously prepared into a synthetic nutritional composition and a pharmaceutical
composition with a higher therapeutic-effect by combining the present COMPOSITION
with other nutritional- and/or pharmaceutical-substances.
[0007] The invention will now be described further by way of example only.
[0008] The present invention is the first to provide SACCHARIDE which comprises neotrehalose,
as well as to provide COMPOSITION which contains neotrehalose as effective component.
[0009] Any preparation of the present SACCHARIDE can be used in the invention, as long as
it produces the present SACCHARIDE. Neotrehalose which is prepared, for example, either
of by the method disclosed in Japanese Patent Laid-Open No.216,492/88, wherein cyclodextrin-synthesizing
enzyme is allowed to act on starch or partial starch hydrolysate, and the method,
disclosed by the present inventors in Japanese Patent Application No.307,054/90, wherein
β-galactosidase is allowed to act on lactoneotrehalose, can be used in the invention
after the treatment of purification.
[0010] Neotrehalose preparations, which have been purified to the possible highest level,
are preferably used in the present SACCHARIDE: Usually, neotrehalose preparations
in the form of syrup or powder with a neotrehalose content of 50 w/w % or higher,
preferably, those in the form of syrup or crystalline powder with a neotrehalose content
of 80 w/w % or higher, more preferably, those in the form of crystalline powder or
crystal with a neotrehalose content of 90 w/w % or higher are suitably used in the
invention.
[0011] Any COMPOSITION can be used in the invention, as long as it contains neotrehalose
as effective ingredient and can supply energy to a living body, and usually, in order
to higher the effect, COMPOSITIONs with a neotrehalose concentration of 10 w/w % or
higher, preferably, 20 w/w % or higher on the dry solid basis (abbreviated as "d.s.b."
hereinafter) can be favorably used in the invention.
[0012] A simple composition consisting of neotrehalose can be used in the invention, and
usually, the present COMPOSITION can be prepared by combining neotrehalose with one
or more of other substances, for example, nutritional substances such as proteins,
amino acids, lipids, other saccharides, vitamins and minerals; and effective substances
such as antibacterial substances, enzymes, hormones and cytokines. If necessary, one
or more of other appropriate substances such as taste-improving agents and coloring
agents, flavor-imparting agents, stabilizers, vehicles and fillers, can be used in
combination, and the COMPOSITION thus obtained can be formed to meet to its final
use.
[0013] The COMPOSITION is orally- and/or parenterally administered without exhibiting toxicity
and fear of causing side effect, and satisfiably metabolized and utilized
in vivo. Thus, the COMPOSITION can be advantageously used to supplement energy to a living
body.
[0014] The dose of the present SACCHARIDE is chosen from the range of about 1-1,000 g/day/adult,
preferably, from the range of about 5-500 g/day/adult based on the weight of neotrehalose,
d.s.b., as effective ingredient.
[0015] The present SACCHARIDE and COMPOSITION are advantageously administrable to human,
as well as to domestic-and pet-animals such as cow, horse, dog and cat.
[0016] The following Experiments will explain the present invention in detail.
Experiment 1
Digestion test in vitro
[0017] In accordance with the method reported in K. Okada et al.,
Journal of Japanese Society of Nutrition and Food Science, Vol.43, No.1, pp.23-29 (1990), a crystalline neotrehalose specimen prepared by the
method in Example A1-2 was prepared into an aqueous solution which was then tested
for its digestibility
in vitro: The digestibility was determined with the following equation and expressed as hydrolysis
rate (%):
The results were as shown in Table 1.
Table 1
|
Hydrolysis rate (%) |
Salivary amylase |
0.0 |
Gastric juice |
0.0 |
Amylopsin |
0.0 |
Enzyme of small intestinal mucous membrane |
43.0 |
[0018] As evident from the results in Table 1, neotrehalose is well digested by the enzyme
from small intestinal mucous membrane.
[0019] Similarly as above, several kinds of disaccharides were tested for their digestibility
using the enzyme from small intestinal mucous membrane.
[0020] The results were as shown in Table 2.
Table 2
|
Hydrolysis rate (%) |
Maltose |
80.1 |
Sucrose |
25.1 |
Isomaltose |
13.2 |
Lactose |
9.7 |
Cellobiose |
1.2 |
Trehalose (α,α-trehalose) |
0.4 |
Neotrehalose (α,β-trehalose) |
43.0 |
Isotrehalose (β,β-trehalose) |
0.1 |
[0021] As evident from the results in Table 2, it was elucidated that unexpectedly next
to maltose, neotrehalose was more digestible by the enzyme from small intestinal mucous
membrane, and the digestibility of neotrehalose was far higher than that of sucrose.
Experiment 2
Utilization test in vivo
Experiment 2-1
[0022] In accordance with the method described in H. Atsuji et al.,
Journal of Clinical Nutrition, Vol.41, Vol.2, pp.200-208 (1972), 30 g of a neotrehalose specimen was prepared into
a 20 w/v % aqueous solution which was then orally administered to 3 healthy volunteers
(26-, 39- and 52-year old men) and their bloods were sampled at prescribed time intervals
and tested for the blood sugar and insulin levels. As control, glucose was used.
[0023] As a result, neotrehalose behaved similarly as glucose, and the maximum values of
both blood sugar and insulin levels were observed about 0.5-1 hour after the oral
administration.
[0024] This confirmed that neotrehalose was readily digested, absorbed, metabolized and
utilized into energy.
Experiment 2-2
[0025] A neotrehalose specimen prepared by the method in Example A1-2 was allowed to remove
pyrogen in an usual manner, and 50 g of the resultant neotrehalose specimen was prepared,
in accordance with the method reported in Matsuzaki,
Yakubutsu Ryoho, Vol.6, No.2, pp.65-72 (1973), into a 10 w/v % aqueous solution which was then intravenously
administered to 2 healthy volunteers (37- and 49-year old men) through instillation
and their bloods were sampled at prescribed time intervals and subjected to the measurements
of the blood sugar and insulin levels and the amount of neotrehalose secreted in their
urine. As control, glucose and maltose were used.
[0026] As a result, glucose extremely increased the blood sugar and insulin levels, while
neotrehalose exhibited the same dynamics as maltose, i.e. neotrehalose slightly increased
the blood sugar level but almost not increased the insulin level. The amount of glucose
in the urines of the volunteers, who had been administered with glucose, was less
than 10%, while those with neotrehalose and maltose were less than 20%. These results
confirm that neotrehalose is a saccharide which is well metabolized and utilized by
a living body, and this renders neotrehalose very useful in SACCHARIDEs and COMPOSITIONs.
Experiment 3
Acute toxicity
[0027] A crystalline neotrehalose specimen, prepared by the method in Example A1-2, was
orally administered to 7 week-old dd mice for acute toxicity test. As a result, no
animal death was noted with the administration of up to 5 g of the specimen, and higher
dose was difficult to do. Therefore, the toxicity of the tested substance appears
to be extremely low.
[0028] The present SACCHARIDE which comprises neotrehalose and the present COMPOSITION which
contains neotrehalose as effective ingredient are illustrated by the following Examples
A and B respectively.
Example A1
Neotrehalose
Example A1-1
Preparation of lactoneotrehalose
[0029] Fifty parts by weight of commercially-available lactose and 50 parts by weight of
"PINE-DEX #1", a dextrin product (DE 8) commercialized by Matsutani Chemical Ind.,
Co., Ltd., Hyogo, Japan, were dissolved in 150 parts by weight of water while heating,
and the solution was heated to 60°C, adjusted to pH 6.0, added with 300 units/g dextrin
of a cyclomaltodextrin glucanotransferase from
Bacillus stearothermophilus commercialized by Hayashibara Biochemical Laboratories Inc., Okayama, Japan, allowed
to react for 20 hours, and heated at 100°C for 30 minutes to inactivate the remaining
enzyme. Thereafter, the mixture was cooled to 55°C, adjusted to pH 5.0, added with
15 units/g dextrin of "Glucozyme", a glucoamylase specimen commercialized by Nagase
Biochemicals Ltd., Kyoto, Japan, allowed to react for 16 hours, and heated at 100°C
for 15 minutes to inactivate the remaining enzyme. The resultant solution containing
about 24 w/w % lactoneotrehalose, d.s.b., was decolored with activated charcoal, treated
with ion exchange (H⁺- and OH⁻-form) for deionization and purification, concentrated
to give a concentration of about 45 w/w % and subjected to column chromatography,
followed by the recovery of lactoneotrehalose-rich fractions. As the fractionating
resin was used "Amberlite XT-1016 (Na⁺-form)", a strongly-acidic cation exchange resin
commercialized by Japan Organo Co., Ltd., Tokyo, Japan, which was suspended in water
and packed in jacketted-stainless steel columns, inner diameter of 5.4 cm each. In
this case, 4 columns, gel-bed depth of 5 m each, were cascaded to give a total gel-bed
depth of about 20 m. While keeping the inner temperature of the columns at 55°C, 5
v/v % of a material saccharide solution was added thereto, and 55°C water was then
passed through the columns at a flow rate of SV 0.3 to effect fractionation, thus
obtaining lactoneotrehalose-rich fractions. A portion of lactoneotrehalose-rich fractions,
lactoneotrehalose content of about 67 w/w %, d.s.b., which had been pooled through
the repetition of the above method, was concentrated to give a concentration of 75
w/w %, and allowed to stand overnight at 20°C to effect crystallization. A high-lactoneotrehalose
content solution, which had been prepared by concentrating the lactoneotrehalose-rich
fractions to give a concentration of 70 w/w %, was added with the resultant crystal
as seed to effect crystallization under gentle-stirring conditions. The resultant
massecuite was separated, and the formed crystal was washed by spraying thereto a
small amount of water to obtain a high-purity crystalline lactoneotrehalose which
was then dissolved in water and treated similarly as above to effect recrystallization.
Thus, about 3 parts by weight of a high-purity crystalline lactoneotrehalose, purity
of 99.8 w/w % or higher, was obtained.
Example A1-2
Preparation of neotrehalose
[0030] One part by weight of a crystalline lactoneotrehalose specimen obtained by the method
in Example A1-1 was dissolved in 30 parts by weight of water while heating, and the
solution was adjusted to 40°C and pH 4.5, added 10 units/g lactoneotrehalose of "LACTASE-LP",
a β-galactosidase specimen commercialized by K·I Chemical Industry, Co., Ltd., Shizuoka,
Japan, allowed to react for 20 hours, and heated at 100°C for 10 minutes to inactivate
the remaining enzyme. Similarly as in Experiment 1, the resultant solution containing
about 66 w/w % neotrehalose and about 33 w/w % galactose, d.s.b., was decolored, deionized,
purified, concentrated, and subjected to column chromatography using a strongly-acidic
cation exchange resin, followed by the recovery of neotrehalose-rich fractions.
[0031] A part of the neotrehalose-rich fractions containing about 88 w/w % neotrehalose,
d.s.b., was concentrated to give a concentration of 75 w/w %, and allowed to stand
overnight at 20°C to effect crystallization. A solution having a concentration of
70 w/w %, which had been prepared by concentrating the neotrehalose-rich fractions,
was added with the resultant crystal as seed to effect crystallization under gentle
stirring conditions. The resultant massecuite was separated, and the formed crystal
was washed by spraying thereto a small amount of water to obtain a high-purity crystal
which was then dissolved in water and recrystallized similarly as above to obtain
about 0.15 parts by weight of a high-purity crystalline neotrehalose, purity of 99.8
w/w % or higher.
[0032] The product is an orally- and/or parenterally-administrable SACCHARIDE. COMPOSITIONs
such as nutritional- and pharmaceutical-compositions can be advantageously prepared
by incorporating thereto the product.
Example A2
Neotrehalose
[0033] A solution containing about 66 w/w % neotrehalose, d.s.b., prepared by using the
reaction- and purification-methods in Example A1-2, as a material saccharide solution,
was concentrated to give a concentration of about 45 w/w %. In order to higher the
neotrehalose content in the resultant solution, which was subjected to column chromatography
similarly as the method in Example A1-1 except that "DOWEX 50W×4 (Ca⁺⁺-form)", a strongly-acidic
cation exchange resin commercialized by Dow Chemical Company, Midland, Michigan, USA,
was used as a resin for fractionation to obtain a neotrehalose-rich fraction containing
about 85 w/w % neotrehalose, d.s.b. The fraction was concentrated to give a concentration
of about 83 w/w %, and the resultant solution was transferred to a crystallizer and
admixed with an about one w/w % seed. The mixture was transferred to a tray and allowed
to stand at 20°C for 4 days to effect crystalization and solidification. Thereafter,
the resultant solid was pulverized with a cutting-type pulverizer and dried to obtain
a crystalline neotrehalose powder containing molasses in the yield of about 70 w/w
%, d.s.b.
Example B1
Chocolate
[0034] Forty parts by weight of cacao paste, 10 parts by weight of cacao butter, and 50
parts by weight of a crystalline neotrehalose specimen obtained by the method in Example
A1-2 were mixed, and the mixture was fed to a refiner to reduce the particle size,
transferred to a conche, and kneaded therein at 50°C for 2 days. In the kneading step,
0.5 parts by weight of lecithin was added and dispersed to homogeneity. Thereafter,
the content was adjusted to 31°C with a thermoregulator, and placed in a mold immediately
before the solidification of the butter, deaerated with a vibrator, and solidified
by passing it through a 10°C cooling tunnel over a period of 20 minutes. The content
was removed from the mold and packaged to obtain the captioned product.
[0035] The product with an excellent color, gloss and texture exhibits no hygroscopicity
and smoothly melts in the mouth to exhibit a moderate sweetness and smooth flavor.
The product can be suitably used as COMPOSITION.
Example B2
Chewing gum
[0036] Three parts by weight of a gum base was melted by heating until it softened, and
admixed with 4 parts by weight of sucrose, 3 parts by weight of a crystalline neotrehalose
powder obtained by the method in Example A2, and adequate amounts of a flavoring agent
and coloring agent. The mixture was kneaded with a roll in an usual manner, formed
and packaged to obtain the captioned product.
[0037] The product is a favorable chewing gum having a satisfiable texture and flavor. The
product can be advantageously used as COMPOSITION.
Example B3
Custard cream
[0038] One hundred parts by weight of corn starch, 30 parts by weight of maltose, 20 parts
by weight of sucrose, one part by weight of salt, and 150 parts by weight of a neotrehalose
syrup prepared by concentrating a solution containing about 66 w/w % of neotrehalose
which had been prepared by the method and purification in Example A1-2 to give a concentration
of about 70 w/w %, were mixed to homogeneity, admixed with 280 parts by weight of
eggs, and gradually added with 1,000 parts by weight of a boiling milk. The mixture
was heated while stirring, and the heating was stopped when the whole content turned
semi-transparent, and the resultant mixture was cooled, added with an adequate amount
of vanilla flavor, weighed, filled up and packaged to obtain the captioned product.
[0039] The product has a smooth gloss, moderate sweetness and satisfiable taste. The product
can be advantageously used as COMPOSITION.
Example B4
"Uiro-no-moto" (premix of sweet rice jelly)
[0040] An uiro-no-moto was prepared by mixing to homogeneity 90 parts by weight of rice
powder, 20 parts by weight of corn starch, 120 parts by weight of a crystalline neotrehalose
powder obtained by the method in Example A2, and 4 parts by weight of pullulan. The
mixture was kneaded with adequate amounts of "matcha" (powdered green tea) and water,
and the resultant mixture was placed in a vessel and steamed up over a period of 60
minutes to obtain an uiro containing matcha.
[0041] The product has a satisfiable gloss, biting-property and flavor. The shelf-life of
the product is relatively long because the retrogradation of starch in the product
is inhibited. The product can be advantageously used as COMPOSITION.
Example B5
Lactic acid beverage
[0042] Ten parts by weight of defatted milk was sterilized by heating at 80°C for 20 minutes,
cooled to 40°C, added with 0.3 parts by weight of a starter, and fermented at about
37°C for 10 hours. Thereafter, the mixture was homogenized and added with 4 parts
by weight of a crystalline neotrehalose powder obtained by the method in Example A2,
one part by weight of sucrose, and 2 parts by weight of an isomerized syrup. The resultant
mixture was sterilized at 70°C, cooled, added with an adequate amount of a flavoring
agent, and bottled to obtain the captioned product.
[0043] The product is a high-quality lactic acid beverage having a sour taste which is satisfactorily
harmonized with flavor and sweetness. The product can be advantageously used as COMPOSITION.
Example B6
Fruit-juice powder
[0044] Thirty-three parts by weight of pulverized orange juice prepared by spray-drying
was stirred and mixed to homogeneity with 50 parts by weight of a crystalline neotrehalose
specimen obtained by the method in Example A1-2, 10 parts by weight of sucrose, 0.65
parts by weight of anhydrous citric acid, 0.1 part by weight malic acid, 0.1 part
by weight of L-ascorbic acid, 0.1 part by weight of sodium citrate, 0.5 parts by weight
of pullulan, and an adequate amount of a powdery flavoring agent. The mixture was
pulverized, and the resultant powder was fed to a fluidized-bed granulator and granulated
at an inlet temperature of 40°C and an air-flow-rate of 150m³/min for 30 minutes while
spraying the content with a high-neotrehalose content solution, obtained by the method
in Example A2, as a binder. Thereafter, the resultant was weighed and packaged to
obtain the captioned product.
[0045] The product is a fruit-juice powder having an orange juice content of about 30 w/w
%. The product is free of an unfavorable taste and odor, and stable over a relatively-long
time period without being solidified by absorbing moisture. The product can be advantageously
used as COMPOSITION.
Example B7
Solid intubation-nutrient
[0046] A composition was prepared by mixing 500 parts by weight of a crystalline neotrehalose
specimen obtained by the method in Example A1-2, 270 parts by weight of dried yolk,
209 parts by weight of defatted milk, 4.4 parts by weight of sodium chloride, 1.85
parts by weight of potassium chloride, 4 parts by weight of magnesium sulfate, 0.01
part by weight of thiamine, 0.1 part by weight of sodium ascorbate, 0.6 parts by weight
of vitamin E acetate, and 0.04 part by weight of nicotinamide. Twenty-five g aliquots
of the composition were distributed into laminated-aluminum small bags, and heat sealed
to obtain the captioned product.
[0047] In use, one bag of the product is first dissolved in an about 150-300 ml water to
prepare an intubation nutrient solution, which is then orally administered or administered
through intubation feeding, for example, into nasal cavity, gullet and stomach. The
product can be advantageously used as COMPOSITION.
Example B8
Infusion solution
[0048] A crystalline neotrehalose specimen prepared by the method in Example A1-2 was dissolved
in water to give a concentration of about 10 w/v %, and the solution was subjected,
in an usual manner, to membrane filtration, aseptically distributed into a plastic
bottle, and sealed to obtain the captioned product.
[0049] The product is a stable agent free of change on standing and can be favorably used
in intravenous- and intraperitoneal-injections which supplement energy to a living
body. The product gives isotonicity at a concentration of 10 w/v % to the blood and
supplies energy to a living body at 2-fold higher concentration than in the case of
glucose.
Example B9
Infusion solution
[0050] A crystalline neotrehalose specimen was dissolved in water to give a concentration
of 20 w/v %, and the solution was subjected, in an usual manner, to membrane filtration,
aseptically distributed into a plastic bag and sealed to obtain the captioned product.
[0051] The product is stable and free of change on standing and can be favorably admixed
with other medicaments and/or COMPOSITIONs and adjusted to an appropriate concentration,
prior to administration.
Example B10
Infusion solution
[0052] A crystalline neotrehalose and a crystalline sorbitol were mixed and dissolved in
water to give concentrations of 5 w/v % and 2.5 w/v % respectively, and the mixture
was distributed, similarly as in Example B8, into a bottle and sealed to obtain the
captioned product.
[0053] The product is stable and free of change on standing and can be favorably used in
intravenous- and intraperitoneal-injections which supplement amino acids and energy
to a living body.
Example B11
Infusion solution
[0054] A crystalline neotrehalose specimen prepared by the method in Example A1-2 and an
amino acid composition having the following components were dissolved in water to
give concentrations of 5 w/v % and 3.0 w/v % respectively, and the mixture was purified,
similarly as in Example B8, distributed into a bag and sealed to obtain the captioned
product.
Components of amino acid composition |
mg/100ml |
L-Isoleucine |
180 |
L-Leucine |
410 |
L-Lysine hydrochloride |
620 |
L-Methionine |
240 |
L-Phenylalanine |
290 |
L-Threonine |
180 |
L-Tryptophan |
60 |
L-Valine |
200 |
L-Arginine hydrochloride |
270 |
L-Histidine hydrochloride |
130 |
L-Glycine |
340 |
[0055] Although the product is a complex agent which contains saccharide and amino acids,
it is stable and free of change on standing because of the non-reducibility of neotrehalose,
and can be favorably used in intravenous- and intraperitoneal-injections. The product
is suitably used as COMPOSITION to supplement both energy and amino acids to a living
body.
Example B12
Infusion solution
[0056] One hundred parts by weight of a 10 w/v % aqueous neotrehalose solution was added
with 5 parts by weight of soybean and 1.5 parts by weight of lecithin from yolk, and
the mixture was subjected to a mixer to obtain a partial homogenate which was then
mixed to homogeneity with a device commercialized by Gaulin Co., U.S.A., under nitrogen
atmosphere and at a pressure of 600kg/cm² into minute droplets of O/W emulsion, average
particle size of 0.2µm or lower. Similarly as in Example B9, the emulsion was distributed
into a bag and sealed to obtain the captioned product.
[0057] Although the product is a complex COMPOSITION which contains a saccharide and lipids,
it is stable and free of change on standing and can be favorably used in intravenous-and
intraperitoneal-injections for COMPOSITION.
Example B13
Infusion solution
[0058] An aqueous solution containing as minerals 0.136 w/v % sodium dihydrogenphosphate,
0.098 w/v % potassium acetate, 0.031 w/v % magnesium chloride hexahydrate, 0.022 w/v
% calcium chloride dihydrate, 1.59 w/v % sodium lactate was prepared by adding and
dissolving the minerals in a 10 w/v % aqueous neotrehalose solution. The aqueous solution
was adjusted to pH 5.5, and distributed, similarly as in Example B9, and sealed to
obtain the captioned product.
[0059] The product is stable and free of change on standing and can be favorably used in
intravenous- and intraperitoneal-injections which supplement energy and minerals to
a living body.
Example B14
Infusion solution
[0060] An aqueous solution containing 0.1 w/v % human serum albumin and 100,000 international
units per ml of human interferon-α was prepared by dissolving human serum albumin
and human interferon-α in a 20 w/v % aqueous neotrehalose solution. The aqueous solution
was subjected to membrane filtration, aseptically distributed into a 10ml-bottle and
sealed to obtain the captioned product.
[0061] The neotrehalose in the product stabilizes the human interferon-α as biologically
active substance, and this renders the activity of the human interferon-α stable for
a relatively-long time period when stored under light-shielded conditions. The product
can be advantageously used to attain a therapeutic effect exerted by the biologically
active substance, as well as to supplement energy to a living body by dissolving the
product in distiled water for injection or by using the product with other COMPOSITION
in combination, prior to use.
Example B15
Traumatic in the form of ointment
[0062] Five hundred parts by weight of a crystalline neotrehalose specimen, prepared by
the method in Example A2, was admixed with 50 parts by weight of a methanol solution
which had been prepared by dissolving 3 parts by weight of iodine in methanol, and
the resultant mixture was admixed with 200 parts by weight of a 10 w/w % aqueous pullulan
solution to obtain the captioned product having an appropriate spreadability and adhesiveness.
[0063] The product exerts an antibacterial action inherent to iodine and acts as COMPOSITION
via the action of neotrehalose, and these shorten the healing time period and cure
the affected part as beautiful as before.
Example B16
Sugar-coated tablet
[0064] A plain tablet (150 mg in weight) as a core tablet was coated with the first sugar-coating
composition consisting of 40 parts by weight of a crystalline neotrehalose specimen
obtained by the method in Example A1-2, 2 parts by weight of pullulan (average molecular
weight of 200,000), 30 parts by weight of water, 25 parts by weight of talc, and 3
parts by weight of titanium oxide until the tablet weighed about 230 mg. Thereafter,
the resultant tablet was first coated with the second sugar-coating composition consisting
of 65 parts by weight of the same crystalline neotrehalose specimen as used in the
above, one part by weight of pullulan (average molecular weight of 200,000) and 34
parts by weight of water, then coated with a wax solution to impart a gloss. Thus,
the captioned product having a gloss and satisfiable appearance was obtained.
[0065] The handleability in the sugar-coating step for the product is satisfactory, and
the product has a satisfiable shock-resistance and retains its quality at a relatively
high-level over a relatively-long time period. The product can be advantageously used
as COMPOSITION.
[Effect of the invention]
[0066] As evident from above, the present SACCHARIDE which comprises neotrehalose is a stable
and non-reducing saccharide, and, entirely different from trehalose (α,α-trehalose)
and isotrehalose (β,β-trehalose) which are similar to neotrehalose, the present SACCHARIDE
has a feature: It is readily metabolized and utilized
in vivo.
[0067] The present COMPOSITION containing neotrehalose as effective ingredient dose not
show reducing properties and has a relatively-high storage stability. Thus, the present
COMPOSITION has a feature of that it is readily preparable into a more favorable synthetic-nutritional-composition
and a pharmaceutical composition with a higher therapeutic-effect by combining the
present COMPOSITION with other nutritional- and/or effective-substances.
[0068] While there has been described what is at present considered to be the preferred
embodiments of the invention, it will be understood that various modifications may
be made therein, and it is intended to cover in the appended claims all such modifications
as fall within the true spirit and scope of the invention.
1. A saccharide for supplementing energy to a living body, which comprises neotrehalose.
2. The saccharide of claim 1, which contains at least 50 w/w % of neotrehalose, d.s.b.
3. The saccharide of claim 1, wherein said neotrehalose is in the form of syrup or powder.
4. The saccharide of claim 1, wherein said neotrehalose is a crystalline neotrehalose.
5. A composition for supplementing energy to a living body, which contains neotrehalose
as effective ingredient.
6. The composition of claim 5, which contains at least 10 w/w % of neotrehalose on the
dry solid basis.
7. The composition of claim 5, which additionally contains one or more members selected
from the group consisting of proteins, amino acids, saccharides, vitamins, minerals,
antibacterial substances, enzymes, hormones, cytokines, and mixtures thereof.
8. The composition of claim 5, which is orally or parenterally administered to human
and animals.
9. The composition of claim 5, which is in the form of infusion solution.
10. The composition of claim 5, the dose of which is in the range of about 1-1,000 g/day/adult
based on the weight of neotrehalose, d.s.b.
11. A process for preparing composition for supplementing energy to a living body which
contains neotrehalose as effective ingredient, said process comprising:
(a) providing an aqueous neotrehalose solution;
(b) purifying the aqueous neotrehalose solution to remove pyrogen; and
(c) distributing the resultant solution into a container.
12. The process of claim 11, wherein said aqueous neotrehalose solution in the step (a)
is prepared by using crystalline neotrehalose.
13. The process of claim 11, wherein said composition has an about 1-40 w/v % of neotrehalose.
14. The process of claim 11, wherein the step (a) additionally contains a step of adding
to the aqueous solution one or more members selected from the group consisting of
proteins, amino acids, saccharides, vitamins, minerals, antibacterial substances,
enzymes, hormones, cytokines, and mixtures thereof.
15. The process of claim 11, wherein said composition is parenterally administered to
human and animals.
16. The process of claim 11, wherein the dose of said composition is in the range of about
1-500 g/day/adult based on the weight of neotrehalose, d.s.b.
17. The process of claim 11, wherein said composition is in the form of infusion solution.